Infection by Simian Virus 40 (SV40) can "transform" normal cells from a number of animals, including man, into cancer cells. This process appears to involve the addition of all or part of the SV40 genome to the cell, suggesting that one or more of the viral genes may be responsible for the shift from the normal to the malignant state. Utilizing the DNA from a number of adenovirus (Ad)-SV40 hybrid viruses, the SV40 portion of each of which has been characterized, we are comparing the SV40- complementary RNA (SR40cRNA) transcribed in a variety of SV40 transformed cell lines in an attempt to identify the SV40 gene(s) responsible for this virus' oncogenic potential. We are also extending our studies of the mechanism of action of interferon, which to date have indicated that interferon blocks the transcription of early SV40cRNA, and are examining the basis for the altered interferon sensitivity of SV40 T antigen synthesis when this early SV40 antigen is induced by Ad-SV40 hybrid viruses. We are in addition examining the effect of purified interferon on the expression of SV40 genes in a number of SV40 transformed cell lines.